Glutathione accelerates osteoclast differentiation and inflammatory bone destruction.

Glutathione accelerates osteoclast differentiation and inflammatory bone destruction. Free Radic Res. 2019 Feb 10;:1-11 Authors: Fujita H, Ochi M, Ono M, Aoyama E, Ogino T, Kondo Y, Ohuchi H Abstract Chronic inflammation associated with bone tissues often destruct bones, which is essentially performed by osteoclasts in the presence of immunoregulatory molecules. Hence, regulating osteoclastogenesis is crucial to develop therapeutics for bone-destructive inflammatory diseases. It is believed that reactive oxygen species (ROS) are involved in RANK ligand (RANKL)-induced osteoclast differentiation, and, therefore, glutathione (GSH), the most abundant endogenous antioxidant, suppresses osteoclast differentiation and bone resorption by RANKL. Interestingly, GSH also contributes to inflammatory responses, and the effects of GSH on osteoclast differentiation and bone destruction under inflammatory conditions have not yet been determined. Here, we investigated how GSH affects inflammatory cytokine-stimulated osteoclast differentiation in vitro and in a mouse model of inflammatory bone destruction. We found that GSH significantly promoted TNFα-stimulated osteoclast formation, while an inhibitor of GSH synthesis, buthionine sulfoximine, suppressed it. GSH facilitated the nuclear localization of the NFATc1 protein, a master regulator of osteoclastogenesis, as well as the expression of osteoclast marker genes in a dose-dependent manner. N-acety...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research